Our brain can be considered as a type of information processing system like a computer, where input signals need to be first detected and properly represented, then integrated for decision-making and output control. A unique feature of the brain as an information processing system lies in its adaptability. Namely, sensory experience-induced neural activities can trigger cascades of molecular and cellular changes in brain circuits, which subsequently alter brain functions and affect behavioral outputs. In healthy individuals, this adaptive process can adjust the brain in response to the demands of the external physical and social environments, and ultimately benefit the survival of individuals. Abnormalities in the adaptation to environmental and social stressors can contribute to the development of a variety of mental disorders, such as schizophrenia and depression. In order to prevent maladaptations and develop pharmacological treatments for mental disorders, it is important to understand the cellular and molecular mechanisms of experience-dependent information processing in brain circuits. We have chosen to use laboratory mice as a model organism to investigate the basic cellular and molecular mechanisms of experience-dependent cortical processing. This organism offers several major advantages for this line of study. First, mice and humans both have about 30,000 genes, and about 99 percent of them are shared. Second, the cellular organization of mouse cerebral cortex is similar to human, and major cortical regions are also homologous. Third, it is possible to perform precise molecular manipulations in specific types of cells in mouse brain, which is required to establish causal relationships between genes, cells, circuits and behaviors. Our lab investigates the mechanisms by which experience-induced molecular changes impact on cortical processing of information, with a particular focus on frontal cortical circuits. Normal executive function in goal-directed behavior depends on the frontal cortex, and functional brain imaging studies have revealed altered frontal lobe activity in response to cognitive challenges in psychiatric patients. However, the mechanisms by which behavioral experiences and specific genetic factors may influence the functional cellular architecture and the developmental trajectory of frontal cortical circuits remain largely unknown. Our recent research progress on these topics is highlighted below. Information about past experience is encoded in specific populations of neurons that communicate with one another by firing action potentials. Persistent firing activity is thought to underlie fundamental brain functions, from holding items in working memory to consolidating acquired information in circuits. To investigate how experience affects persistent firing of frontal cortical neurons, we used the promoter of the activity-regulated cytoskeletal protein (Arc) to drive GFP expression, thus labeling neurons that were activated when mice learned a skill. We found that motor training increases Arc expression in subsets of excitatory neurons. Those neurons exhibit persistent firing in contrast to Arc-negative neurons from the same mice or neurons from the untrained mice. Furthermore, in mice carrying genetic deletion of Arc, the frontal cortical circuitry is still in place to initiate experience-dependent gene expression, but the level of persistent firing thereafter is diminished. Finally, our results showed that the emergence of persistent activity is associated with Arc-dependent changes in the function of NMDA-type glutamate receptors, rather than changes in AMPA-type receptors or membrane excitability. Our findings therefore reveal an Arc-dependent molecular pathway by which geneexperience interaction regulates the emergence of persistent firing patterns in specific neuronal populations. Midbrain dopaminergic neurons affect numerous brain processes via different projections and firing patterns. Neurons in the ventral tegmental area fire phasically in response to reward-associated or motivationally salient stimuli, and their projections to the frontal cortex are involved in the control of motivated behavior. The development of the mesofrontal dopaminergic circuit continues into adolescence, and deficiencies in this circuit are associated with adolescent-onset psychiatric disorders in humans. To investigate whether the structure and function of this circuit are modifiable by activity in dopaminergic neurons during adolescent development, we conducted optogenetic stimulation and in vivo two-photon imaging in mice. We found that phasic, but not tonic, dopamine neuron activity induces the formation of dopaminergic axonal boutons in the adolescent frontal cortex. In adult mice, the effect of phasic activity is diminished, but inhibition of dopamine D2-type receptors restores this plasticity. Furthermore, phasic activation of dopamine neurons also induces greater changes in mesofrontal circuit activity and psychomotor response in adolescent mice than in adult mice. Together, our findings demonstrate that the structure and function of the mesofrontal circuit are modifiable by phasic activity in dopaminergic neurons during adolescence and suggest that the greater plasticity in adolescence may facilitate activity-dependent strengthening of dopaminergic input and improvement in behavioral control.